Abstract
The ventral tegmental area dopamine (DA VTA) neurons have the spontaneous tonic activity and an alteration of firing pattern from tonic to burst accelerates dopamine transmission more effectively in the mesoaccumbal dopaminergic system, leading to the reinforcing process of drugs of abuse such as alcohol and nicotine. In the present study, we examined whether a persistent Na+ current would contribute to burst firing in DA VTA neuronsusing nystatin-perforated recording. Tetrodotoxin (TTX) (1 μM) or riluzole (10 μM) hyperpolarized the membrane potential and stopped spontaneous firing of DA VTA neurons. In voltage-clamp analysis, a TTX and riluzole-sensitive and persistent Na+ current was activated at ?60 mV and reached maximal amplitude at ?40 mV. This persistent Na+ current was potentiated by a negative shift of the voltage of activation by eliminating Ca2+ from the extracellular solution. The Ca2+-free extracellular solution depolarized the membrane potential and increased the firing frequency of DA VTA neurons. When a continuous hyperpolarizing current was injected, the firing pattern of the DA VTA neurons transformed into burst-like firing; with average spike number of 4.9, average inter-spike interval of 221 ms, and an average plateau potential, on which the train of spikes generated, was 11 mV. The burst-like firing of DA VTA neurons was abolished by 10 μM riluzole. The concurrent blockade of both T-type Ca2+ current and small conductance Ca2+-activated K+(SK) currents by 100 μM nickel did not induce burst-like firing with or without continuous hyperpolarizing current injection in DA VTA neurons. In conclusion, increases in a persistent Na+ current that mediates a depolarizing driving force by removing extracellular Ca2+ contributes to burst-like firing in DA VTA neurons.
Highlights
Ventral tegmental area dopamine (DA VTA) neurons project their axons to the nucleus accumbens (NAcb) [1]
Our findingsindicate that persistent Na+ current is activated at subthreshold membrane potentials and has a critical role in action potentials (APs) generation in DA VTA neurons, supporting the findings of a previous study in midbrain dopamine neurons [42]
The Ca2+-free extracellular solution potentiated persistent Na+ currents by a negative shift of the activation voltage by 3.5 mV without changing the slope factor, indicating that persistent Na+ current in the Ca2+-free extracellular solution can be activated by negative membrane potentials between −63.5 mV and −43.5 mV
Summary
Ventral tegmental area dopamine (DA VTA) neurons project their axons to the nucleus accumbens (NAcb) [1]. The properties of burst firing have been studied in midbrain dopamine neurons in vitro (brain slice preparations) as well as in vivo [17] [18]. Both excitatory synaptic activity and intrinsic ionic mechanisms are considered to contribute to the burst firing of DA VTA neurons. It is likely that L-type Ca2+ current contributes to the depolarizing driving force that induces burst firing and the SK current counters this L-type Ca2+ channel-mediated depolarizing driving force to prevent burst firing in midbrain dopamine neurons
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